Inoculation of mice with Friend murine leukemia virus (F-MuLV) induces leukemia in erythroid, myeloid and lymphoid lineages. Our previous data indicated that dualtropic recombinant Friend MCF (F-MCF) viruses generated in vivo after F-MuLV inoculation were not required for myeloid or lymphoid leukemogenesis. However, in certain mouse strains there was a strong correlation between expression of F-MCF viruses and erythroid leukemia. Possible leukemogenic effects of F-MCF viruses isolated free of F-MuLV were studied by inoculation of newborn mice. Only 2 of 12 isolates were leukemogenic. These two isolates induced mostly erythroid leukemia, though occasional lymphoid and myeloid leukemias were observed. Surprisingly, the latent period was longer with F-MCF viruses than with F-MuLV. Furthermore, inoculation of F-MCF at birth followed by F-MuLV at 6 weeks caused an accelerated appearance of leukemias. The most likely interpretation of these results is that phenotypic mixing of envelopes and RNAs of these two viruses leads to more rapid infection of cell types which are highly susceptible to leukemic transformation.